Neoplasms

 Angiogenesis, metastasis and invasion

 Replicative potential:

Most of the human cells have the ability to divide up to 60 times, after that become senescent  they lose the ability to replicate . This phenomenon is given by a progressive shortening of telomeres at the ends of the chromosome, which are recognized by the machinery of DNA repair , p53 and RB, as areas of breakage dsDNA, this allows detention cell cycle .

In cells where the original control points are altered as cancer, the rescue via non-homologous end joining is activated , this leads to the formation of dicentric chromosomes, which later in anaphase phase separate

Telomerase, meanwhile is inactive in somatic cells , in cancer cells has high activity, this enzyme 's function telomere elongation, which in turn facilitate a doubling of these cells.

Angiogenesis:

Solid tumors can´t grow more than 1 or 2 mm in diameter if they are not vascularized, these require the contribution of O2 , nutrients and exchange of waste products .

Cancer cells can stimulate angiogenesis during which new vessels arise from existing ones.

Cancer cells can stimulate angiogenesis during which new vessels arise from existing ones. 

This vascular neofromación has a dual effect on tumor growth : allowing good tumor perfusion , carrying nutrients and O2 , and moreover , the adjacent newly formed endothelial cells to stimulate tumor cell growth, secretion of growth factors , among these are:

-FGI

-Colony stimulating factor granulocyte / macrophage

-PDGF

Proteases are enzymes which are released by tumor cells or by stromal cells in response to the presence of tumor, are involved in the regulation of angiogenic and anti-angiogenic factors.

Proteases are enzymes which are released by tumor cells or by stromal cells in response to the presence of tumor, are involved in the regulation of angiogenic and anti-angiogenic factors

colony stimulating -factor granulocyte / macrophage

These proteases can release growth factors such as :

-bFGF , sequestered in the ECM

They can also release angiogenic factors such as:

-angiostatina

-vasculostatina

-endostatina

Produced from the degradation of plasminogen and collagen trasnterritina respectively in the cellular matrix

Other angiogenic agent , such as HIF 1 , released by hypoxic cells induces angiogenesis by an increase in the expression of VEGF and bFGF , which allow the proliferation of endothelial cells and allow their development towards the tumor.

In normal cells these angiogenic factors are regulated by genes such as p53 or BB which are mutated in cancer, example of this regulation have that p53 stimulates the production of an anti-angiogenic factor and thrombospondin - 1 represses expression of molecules angiogenic as VEGF .

Invasion and metastasis 

Invasion and metastasis are biological markers of malignancy , a tumor mass to be released from a primary to a secondary mass distal location , require a series of steps , comprising two stages:

-extracellular matrix -invasion

-vascular dissemination, accommodation tumor cells and colonization.

  Extracellular matrix -invasion

     

   

Normal cells are adhered to each othe , and have cell-cell interaction by binding proteins such as E- cadherin,  which in turn bind to catenin which are anchored to the cytoskeleton. A negative expression of the ability of cells to adhere to one another occurs , and facilitates the release of the primary tumor .

Tumor cells, degrade the extracellular matrix , by the release of proteases, this allows in turn the release of growth factors in ECM . , Example of these enzymes have the degrading metalloproteinase 9 type 4 collagen,  and stimulates VEGF release .

These cells bind to receptors such as laminin , the collagens type 4 , fibronectin , finally we locomotion , given by factors released by tumor cells motility auticrino factor and growth factor - factor disperser by hepatocyte cells stroma .

Vascular dissemination, accommodation tumor cells and colonization:

Tumor cells in the circulation , tend to aggregate in groups . This is favored by homotypic adhesions between tumor cells and by heterotypic adhesion between tumor cells and blood cells , primarily platelets, also bind to the coagulation factor activated and form a emboli.

The formation of platelet - tumor aggregates may enhance survival , extravasation of tumor emboli located distant involves adhesion to the endothelium followed by discharge through the basal menbran . In these processes as adhesion molecules involved :

-Integrinas

-Lamininas

-Mainly CD44 , which is expressed on the membrane of T cells , most metástais appear in the first capillary bed available to the tumor.